Female urinary incontinence is a common medical problem which affects a large number of women, particularly in the postmenopausal age, and which causes extensive social, psychological and financial problems. It is responsible for 40-60% of all nursing home admissions and entails an annual estimated cost of $8 billions. The integral theory of female urinary stress incontinence of Petros and Ulmsten emphasizes the role of reduced tensile properties of the vagina in contributing to incontinence. Our hypothesis to be tested in the present study is that incontinence is related to alterations and weakening of the connective tissue of the vesico-vaginal fascia and other supporting structures: the fascia provides tensile support to the vagina and bladder and the connective tissue structures of the urethral wall and tendinous muscle attachments may participate in the bladder sphincter mechanism. Our studies will focus on the fascia because this tissue is excised as a residual tissue during surgical treatment of cystocele and/or urinary incontinence. Tissues from patients with cystocele, but not incontinence, will serve as controls. The first (and major) aim will be to study the biochemical features of the vesico-vaginal fascia that might contribute to its possible biomechanical weakness. The content of interstitial collagen (types I + III) will be determined by hydroxyproline assay to see if the fascia is deficient in this tensile element. The crosslinking of collagen will be explored in two ways - by (1) its solubility in 0.5 M acetic acid and after mild pepsin digestion and by (2) direct quantitation of the permanent nonreducible crosslink, pyridinoline. Collagenase, a protease that is specific for the degradation of collagen, will be assayed in tissue specimens as a check on a possible degradative mechanism that would weaken the connective tissues. In view of the widespread use of estrogen treatment for incontinence, the second aim will be to quantitate the level of estrogen receptors in the fascia. This will be done by RIA. If receptors are present in normal amount this would provide a firmer basis for continuing studies of estrogen supplementation. Overall, these studies should help to establish, or to disprove, the hypothesis that connective tissue changes are important in the onset of incontinence.